title: Glycoproteomic analysis of bronchoalveolar lavage (BAL) fluid identifies tumor-associated glycoproteins from lung adenocarcinoma.
abstract: Cytological examination of cells from bronchoalveolar lavage (BAL) is commonly used for the diagnosis of lung cancer. Proteins released from lung cancer cells into BAL may serve as biomarkers for cancer detection. In this study, N-glycoproteins in eight cases of BAL fluid, as well as eight lung adenocarcinoma tissues and eight tumor-matched normal lung tissues, were analyzed using the solid-phase extraction of N-glycoprotein (SPEG), iTRAQ labeling, and liquid chromatography tandem mass spectrometry (LC-MS/MS). Of 80 glycoproteins found in BAL specimens, 32 were identified in both cancer BAL and cancer tissues, with levels of 25 glycoproteins showing at least a 2-fold difference between cancer and benign BAL. Among them, eight glycoproteins showed greater than 2-fold elevations in cancer BAL, including Neutrophil elastase (NE), Integrin alpha-M, Cullin-4B, Napsin A, lysosome-associated membrane protein 2 (LAMP2), Cathepsin D, BPI fold-containing family B member 2, and Neutrophil gelatinase-associated lipocalin. The levels of Napsin A in cancer BAL were further verified in independently collected 39 BAL specimens using an ELISA assay. Our study demonstrates that potential protein biomarkers in BAL fluid can be detected and quantified.
authors.affiliation: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA. qli23@jhmi.edu
authors.forename: Qing Kay
authors.initials: QK
authors.lastname: Li
authors.forename: Punit
authors.initials: P
authors.lastname: Shah
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Paul O
authors.initials: PO
authors.lastname: Aiyetan
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Rex
authors.initials: R
authors.lastname: Yung
authors.forename: Daniela
authors.initials: D
authors.lastname: Molena
authors.forename: Edward
authors.initials: E
authors.lastname: Gabrielson
authors.forename: Frederic
authors.initials: F
authors.lastname: Askin
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Chan
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000302:isolation & purification*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002853:Chromatography, Liquid; D005260:Female; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics / Q000302:isolation & purification*; D006651:Histocytochemistry; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000302:isolation & purification*; D020543:Proteome / Q000235:genetics / Q000302:isolation & purification*; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; D006023:Glycoproteins; D009363:Neoplasm Proteins; D020543:Proteome